Validity, reliability, and transcultural adaptations of the Bayley Scales of Infant and Toddler Development (BSID-III-NL) for children in Suriname.

BACKGROUND: A valid and reliable measure of infant neurodevelopment is needed in Suriname, South America. The Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III), was created for evaluation of United States infants and toddlers and subsequently validated for use in Dutch speaking infants of the Netherlands (BSID-III-NL). Given that Suriname was a previous Dutch colony and Dutch remains the national language of Suriname, this study sought to evaluate the psychometric properties of the BSID-III-NL in Suriname. AIMS: Given that the cultural context differs between Suriname, the United States, and the Netherlands, the aims of this study were to determine if any cultural adaptations of the BSID-III-NL were needed for Surinamese infants and to evaluate its psychometric properties. METHODS: Two hundred and ninety-nine infants between the ages of 10 to 26 months were assessed in three geographic regions of Suriname between May 2018 and July 2019. Minor adaptations to the BSID-III-NL imagery were made based on the input of Surinamese pediatricians and neuropsychologists who were also involved in the administration of the BSID-III-NL in Suriname. Raw scores were collected for the cognitive, communicative, and motor subscales of the BSID-III-NL. Factor structure was evaluated with exploratory factor analysis and cluster analysis, and reliability of internal consistency was assessed using Cronbach's alpha coefficient for each subscale. RESULTS: Content validity was endorsed by pediatricians and neuropsychologists in Suriname who participated in the administration of the BSID-III-NL. Construct validity was demonstrated through agreement of items from cluster analysis where at least 81.56% of all variability was explained by clustering with correct or incorrect responses and mean raw scores in subscales increased with age group. Cronbach's alpha coefficient was above 0.77 for all subscales. CONCLUSIONS: This internationally validated developmental measure was found to be valid and reliable in assessing neurodevelopment of infants in Suriname.

Comparison of galantamine and donepezil for effects on nerve growth factor, cholinergic markers, and memory performance in aged rats.

This study was designed to determine 1) whether repeated exposures to the acetylcholinesterase inhibitors (AChEIs) galantamine (GAL) or donepezil (DON) resulted in positive effects on nerve growth factor (NGF) and its receptors, cholinergic proteins, and cognitive function in the aged rat, and 2) whether GAL had any advantages over DON given its allosteric potentiating ligand (APL) activity at nicotinic acetylcholine receptors. Behavioral tests (i.e., water maze and light/dark box) were conducted in aged Fisher 344 rats during 15 days of repeated (subcutaneous) exposure to either GAL (3.0 or 6.0 mg/kg/day) or DON (0.375 or 0.75 mg/kg/day). Forty-eight hours after the last drug injection, cholinergic receptors were measured by [(125)I]-(+/-)-exo-2-(2-iodo-5-pyridyl)-7-azabicyclo[2.2.1]heptane ([(125)I]IPH; epibatidine analog), (125)I-alpha-bungarotoxin ((125)I-BTX), [(3)H]pirenzepine ([(3)H]PRZ), and [(3)H]-5,11-dihydro-11-[((2-(2-((dipropylamino)methyl)-1-piperidinyl)ethyl)amino)carbonyl]-6H-pyrido(2,3-b)(1,4)-benzodiazepin-6-one methanesulfonate ([(3)H]AFDX-384, or [(3)H]AFX) autoradiography. Immunochemical methods were used to measure NGF, high (TrkA and phospho-TrkA)- and low (p75 neurotrophin receptor)-affinity NGF receptors, choline acetyltransferase (ChAT), and the vesicular acetylcholine transporter (VAChT) in memory-related brain regions. Depending on dose, both GAL and DON enhanced spatial learning (without affecting anxiety levels) and increased [(125)I]IPH, [(3)H]PRZ, and [(3)H]AFX (but decreased (125)I-BTX) binding in some cortical and hippocampal brain regions. Neither AChEI was associated with marked changes in NGF, NGF receptors, or VAChT, although DON did moderately increase ChAT in the basal forebrain and hippocampus. The results suggest that repeated exposures to either GAL or DON results in positive (and sustained) behavioral and cholinergic effects in the aged mammalian brain but that the APL activity of GAL may not afford any advantage over acetylcholinesterase inhibition alone.

Chronic exposure to typical or atypical antipsychotics in rodents: temporal effects on central alpha7 nicotinic acetylcholine receptors.

A decrease in alpha7 nicotinic acetylcholine receptors in the hippocampus has been hypothesized to contribute to alterations in auditory gating and other behavioral impairments in schizophrenia. However, while both typical and atypical neuroleptics are routinely used in the therapeutics of schizophrenia, little is known about their effects on auditory gating or alpha7 nicotinic acetylcholine receptor expression particularly when they are administered for extended periods of time (which is common in the clinical setting). In the present study in normal rats, the residual effects of prior chronic treatment (90 or 180 days) with representative typical and atypical neuroleptics (oral haloperidol, 2.0 mg/kg/day; chlorpromazine, 10.0 mg/kg/day, risperidone, 2.5 mg/kg/day; or olanzapine, 10.0 mg/kg/day) on prepulse inhibition of the auditory gating response were investigated. The densities of alpha7 nicotinic acetylcholine receptors were subsequently measured using [125I]-alpha-bungarotoxin autoradiography. The results indicated that none of the compounds significantly altered the startle amplitude or prepulse inhibition response either during drug treatment (day 60) or after 90 or 180 days of treatment (i.e. during a drug free washout). However, prior exposure to chlorpromazine, risperidone and olanzapine for 90 days resulted in modest but significant (P<0.01) decreases in [125I]-alpha-bungarotoxin binding sites in some brain regions (e.g. posterior cortical amygdala). After 180 days of treatment, decreases in [(125I]-alpha-bungarotoxin binding ranging from approximately 12% (lateral dentate gyrus) up to 24% (e.g. CA1 hippocampal region) were evident in the risperidone group in 13 of the 36 regions analyzed while decreases associated with the other neuroleptics agents were still present, but not statistically significant. These data indicate that the commonly used atypical neuroleptic, risperidone is associated with time dependent and persistent negative effects on an important biological substrate of memory (i.e. the alpha7 nicotinic receptor), but that the magnitude of the deficits was not sufficient to impair auditory gating.

Dose verification for patients undergoing IMRT.

At Emory Clinic intensity-modulated radiation therapy (IMRT) was started by using dynamic multileaf collimators (dMLC) as electronic tissue compensators in August 1998. Our IMRT program evolved with the inclusion of a commercially available inverse treatment planning system in September 1999. While the introduction of electronic tissue compensators into clinical use did not affect the customary radiation oncology practice, inverse treatment planning does alter our basic routines. Basic concepts of radiation therapy port designs for inverse treatment planning are different from conventional or 3D conformal treatments. With inverse treatment planning, clinicians are required to outline a gross tumor volume (GTV), a clinical target volume (CTV), critical normal structures, and to design a planning target volume (PTV). Clinicians do not designate the volume to be shielded. Because each IMRT radiation portal is composed of many beamlets with varying intensities, methods and practice used to verify delivered dose from IMRT portals are also different from conventional treatment portals. Often, the validity of measured data is in doubt. Therefore, checking treatment planning computer output with measurements are confusing and fruitless, at times. Commissioning an IMRT program and routine patient dose verification of IMRT require films and ionization chamber measurements in phantom. Additional specialized physics instrumentation is not required other than those available in a typical radiation oncology facility. At this time, we consider that routine quality assurance prior to patient treatments is necessary.

Benign parotid hypertrophy on +HIV patients: limited late failures after external radiation.

PURPOSE: Although 8-10 Gy of external radiation therapy for +HIV associated parotid hypertrophy has achieved high response rates, the responses were transient with only 1/12 of patients retaining cosmetic control at median follow-up procedures of 9.5 months. Retreatment for failures after 8-10 Gy has also been unsatisfactory. Having shown that 24 Gy of external radiation therapy for benign parotid hypertrophy produced more durable cosmetic control than 8-10 Gy, we now report on longer follow-up periods on a group of patients receiving 24 Gy. MATERIALS AND METHODS: Twenty +HIV patients with clinical and radiographic evidence of lymphoepithelial lesions of the parotid were treated with 24 Gy of external radiation therapy using daily 1.5 Gy fractions; parallel opposed technique and 6 MV photons were used in 19 patients, and unilateral electron treatment was performed for one patient. RESULTS: With a mean follow-up period of 24 months, the cosmetic control appears durable. We have had no late failures past 24 months. Two patients have complained of modest xerostomia. There was no correlation with size of the cyst and eventual cosmetic result. CONCLUSIONS: Twenty-four Gy produces durable parotid control for HIV associated lymphoepithelial lesions of the parotid glands in +HIV patients. Failures after 2 years are uncommon and the side effects have been tolerable.

'Loop' domain deletional mutant of Bcl-xL is as effective as p29Bcl-xL in inhibiting radiation-induced cytosolic accumulation of cytochrome c (cyt c), caspase-3 activity, and apoptosis.

PURPOSE/OBJECTIVE: To investigate the effect of the enforced expression of p29Bcl-xL or its loop deletional mutant, p18Bcl-xLdelta, on irradiation-induced apoptosis and cell-cycle distribution of HL-60 cells. MATERIALS & METHODS: We compared the irradiation-induced molecular cascade of apoptosis in control human AML HL-60/neo versus Bcl-xL overexpressing (approximately 8-fold) (HL-60/Bcl-xL) and HL-60/Bcl-XLdelta cells that express the loop domain deletional mutant construct (delta26-83 AA) of Bcl-xL. The three cell lines were irradiated with 6MV photons to varying doses up to 20 Gy. Following this, cytosolic cyt c levels, caspase-3 activity, and the Bcl-2 family of proteins were evaluated utilizing Western blot analysis (whole cell lysate or cytosolic S-100 fraction). Apoptosis was assessed by internucleosomal DNA fragmentation, Annexin-V staining and FACS analysis, as well as by morphologic criteria. The cell-cycle effects of radiation were analyzed by flow cytometry. RESULTS: Eight hours following irradiation (12 Gy) of HL-60/neo cells, a marked increase (approximately 8-fold) in the cytosolic accumulation of cyt c in the S-100 fraction was observed. This was associated with the cleavage of caspase-3, as well as the generation of its poly (ADP-ribose) polymerase (PARP) and DFF (DNA fragmentation factor)-45 cleavage activity. Twenty-four to forty-eight hours after irradiation, internucleosomal DNA fragmentation and positive Annexin-V staining (32.3+/-3.3%) was detected in HL-60/neo cells. In contrast, in both HL-60/Bcl-xL and HL-60/Bcl-xLdelta cells, a significantly lower percentage of apoptotic cells (p<0.05) were detected and internucleosomal DNA fragmentation was not induced. Following irradiation, Western analysis neither demonstrated any significant alteration in Bcl-2, p29Bcl-xL, p18Bcl-xLdelta, or Bax; nor induced CD95 (Fas receptor) or Fas ligand expression in any cell type. However, in all cell types, irradiation produced approximately a 2-fold increase in the percentage of cells in the G2/M phase of the cell cycle. CONCLUSION: These results demonstrate that an intact loop domain is not necessary for the full antiapoptotic function of Bcl-xL against irradiation-induced cytosolic accumulation of cyt c, caspase activation, and apoptosis of HL-60 cells. Additionally, the cell-cycle effects of ionizing radiation in HL-60 cells are not affected by enforced expression of Bcl-xL or Bcl-xLdelta.

Anatomic variation of extrahepatic biliary tree structures: importance in treatment planning for radiation therapy.

PURPOSE: To demonstrate the variable location of biliary tree components and to assess two treatment planning rules of thumb used for locating porta hepatic nodes for radiation therapy. MATERIALS AND METHODS: The distance of the common hepatic duct bifurcation and duodenal papilla from adjacent vertebral bodies was measured on 34 cholangiograms, and their relationships to particular vertebral body levels were recorded. Adequacy of treatment volume to encompass porta hepatic lymph nodes was evaluated in 30 of these cholangiograms by constructing radiation portals according to the two rules of thumb. RESULTS: Location of the common hepatic duct bifurcation and duodenal papilla varied widely. The treatment portal encompassed 13% (four of 30) of cases when the first rule of thumb was used and 80% (24 of 30) of cases when the second rule of thumb was used. CONCLUSION: The wide variability of location of extrahepatic biliary tree structures suggests the need for individualized treatment planning so that sensitive and dose-limiting healthy tissues can be optimally excluded from radiation treatment portals. Computed tomography and other imaging modalities enable precise location of biliary tree components for radiation treatment planning.

A totally integrated simulation technique for three-field breast treatment using a CT simulator.

A method was devised to simulate patients with breast cancer in the actual treatment position utilizing a diagnostic CT spiral scanner, 3-D Image Workstation for virtual simulation, and a laser coordinate system to transfer planning parameters to the patient's skin. It was desired to produce non-divergent tangential beams through the lung as well as a matched line for tangential and supraclavicular fields. The patients were immobilized in an Alpha CradleTM cast. Radio-opaque markers were placed on the superior, inferior, medial, and lateral margins of the field so as to afford appropriate initial field set-up approximations. The patient was scanned. The data set was then transferred to the workstation where an isocenter was chosen. The patient was marked. Virtual simulation was then performed. This method employed a half beam technique for the posterior edge of the tangential fields. Table rotation and blocking of the superior margin of the tangential fields were used to produce a vertical edge to match a supraclavicular field. Using a beam's eye view the lateral tangent was matched to the medial exit. A digitally reconstructed radiograph was created to define the tangent fields and place the supraclavicular block. Our initial experience with 50 patients verifies that this is a reproducible and accurate technique. Time required for immobilization and tangential field simulation is approximately 30 minutes. Data is available for 3-D treatment planning or 2-D treatment planning on a reconstructed transverse slice angled to match the collimator angle through the patient. Using a CT simulator for simulation of breast cancer affords accuracy of at least equal magnitude to conventional simulators as determined by beam films and ease of set-up. This technique also affords greater ease in changing treatment parameters without having to resimulate the patient.

Conservative treatment of early-stage breast cancer in a medically indigent population.

The compliance with a program of breast-conservation treatment for early-stage breast cancer and the results of that treatment among women treated between January 1983 and January 1992 was investigated in a large inner-city public hospital serving a primarily black population. Medical records and charts were reviewed for 25 consecutive patients with stage I and II breast cancer seen in consultation in the radiation oncology department. Of those 25 patients, 20 underwent lumpectomy and radiation therapy. Survival, disease-free survival, and local recurrence-free survival were computed using the Kaplan-Meier method. Compliance was evaluated based on time to complete the prescribed course of radiotherapy after a lumpectomy. Five-year local recurrence-free survival for stage I and II patients was 95% (confidence interval [CI]: 71% to 99%). Five-year overall survival for stage II patients was 71% (CI: 31% to 92%), and disease-free survival was 74% (CI: 36% to 91%). This study demonstrates that a program of breast-conservation treatment for early-stage breast cancer can be implemented with good results, excellent treatment compliance, and 100% follow-up in a population of medically indigent women.

Definitive radiation therapy for extrahepatic bile duct carcinoma.

PURPOSE: To evaluate retrospectively the role of radiation therapy for extrahepatic bile duct (EHBD) carcinoma. MATERIALS AND METHODS: Twenty-seven patients with local-regional EHBD carcinomas were treated with definitive radiation therapy. Radiation therapy was delivered by means of external beam radiation therapy (EBRT) alone or combined with transcatheter iridium-192 brachytherapy. The median total dose was 54 Gy (range, 30-144 Gy). Survival rates were calculated and compared by using the log-rank test. Possible prognostic factors affecting survival were evaluated by means of univariate analysis. RESULTS: The median survival of all patients was 13 months, with 1- and 2-year actuarial survival rates of 52% and 10%, respectively. Univariate analysis revealed that men, patients with tumors limited to the bile duct, and patients receiving EBRT doses of at least 45 Gy had significantly better outcomes. Local-regional recurrence was the main cause of treatment failure (82%). Two patients developed gastric outlet obstruction. CONCLUSION: Patients with locally advanced EHBD carcinomas have a low survival rate. Certain factors, however, appear to have prognostic significance.

Fast-neutron therapy in advanced head and neck cancer: a collaborative international randomized trial.

PURPOSE: To compare the efficacy of fast-neutron radiotherapy with that of conventionally fractionated photon therapy in the management of patients with locally advanced squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: Patients with Stage III or IV disease were randomized to receive either 20.4 Gy/12 fractions/4 weeks of neutrons or 70 Gy/35 fractions/7 weeks of photons (control). Between April 1986 and March 1991, 178 patients were entered, 169 of whom were eligible for analysis. The treatment arms were balanced for age, stage, and performance status, but not for primary site of origin. RESULTS: Complete response occurred in 70 and 52% with neutrons and photons, respectively (p = 0.006). Local regional failure at 3 years for all patients was 63% for neutrons and 68% for photons. Actuarial overall survival curves were virtually identical in both study arms, falling to 27% at 3 years. Acute toxicity was similar in the two arms, but late grade 3-5 toxicity was 40% with neutrons compared to 18% with photons (p = 0.008). CONCLUSION: Although the initial response rate was higher with neutrons, permanent local control and survival were not improved, and the incidence of late normal tissue toxicity was increased. As a result, fast-neutron therapy for advanced squamous cell carcinoma of the head and neck can only be recommended for patients in whom the logistic benefit of treatment in 12 sessions over 4 weeks outweighs the increased risk of late toxicity.

Low-dose radiotherapy for multicystic benign lymphoepithelial lesions of the parotid gland in HIV-positive patients: long-term results.

BACKGROUND: Multicystic benign lymphoepithelial lesions of the parotid gland (BLL) seen in patients with human immunodeficiency virus (HIV) can produce considerable cosmetic deformity as well as physical discomfort. We previously reported our preliminary results with low-dose radiotherapy in this disease, and all 8 patients were satisfied with the initial improvement in their appearance. We now report the long-term follow-up of those patients and additional patients. METHODS: Twelve HIV-positive patients with BLL were treated with 8-10 Gy of external radiation using 2-Gy daily fractions. Objective responses and subjective duration of patient-defined cosmetic control were recorded. RESULTS: All 12 patients (100%) had at least a 50% decrease in the size of their parotid masses. Five of 12 (42%) had a complete response and 7 (58%) had a partial response. Persisting complete response was achieved in only 1 patient, however, with relapse in the other 11 patients. Cosmetic palliation, as judged by the patients, was achieved for a median of 9.5 months. Eight patients were subsequently retreated with doses of 6-16 Gy (median and mode: 10 Gy). None (0%) of the 8 patients retreated achieved local control. CONCLUSIONS: Very low-dose radiation (8-10 Gy) provides reliable but temporary cosmetic palliation for BLL. Retreatment was unsatisfactory, and we are now investigating higher initial doses of radiation to prolong palliation and eliminate recurrences.

Photon versus fast neutron external beam radiotherapy in the treatment of locally advanced prostate cancer: results of a randomized prospective trial.

PURPOSE: To evaluate the effectiveness of fast neutron radiation therapy in treatment of locally advanced carcinomas of the prostate. METHODS AND MATERIALS: From April 1986 to October 1990, 178 patients were entered on a prospective, multi-institutional randomized study of the NCI-sponsored Neutron Therapy Collaborative Working Group. This trial compared external beam photon irradiation (7000-7020 cGy) with external beam neutron irradiation (2040 ncGy) for patients with high-grade T2 or T3-4, N0-1, M0 adenocarcinomas of the prostate. Eighty-nine patients were randomized to each treatment. Six patients were subsequently judged to be ineligible, leaving 85 photon and 87 neutron randomized patients eligible for analysis. RESULTS: With a follow-up time ranging from 40 to 86 months (68 months median follow-up) the 5-year actuarial clinical local-regional failure rate for patients treated with neutrons was 11%, vs. 32% for photons (p < 0.01). Incorporating the results of routine posttreatment prostate biopsies, the resulting "histological" local-regional tumor failure rates were 13% for neutrons vs. 32% for photons (p = 0.01). To date, actuarial survival and cause-specific survival rates are statistically indistinguishable for the two patient cohorts, with 32% of the neutron-treated patient deaths and 41% of the photon-treated patient deaths caused by prostate cancer (p = n.s.). Prostate specific antigen (PSA) values were elevated in 17% of neutron-treated patients and 45% of photon-treated patients at 5 years (p < 0.001). Severe late complications of treatment were higher for the neutron-treated patients (11% vs. 3%), and were inversely correlated with the degree of neutron beam shaping available at the participating institutions. Neutron treatment delivery utilizing a fully rotational gantry and multileaf collimator did not result in an increase in severe late effects when compared to photon treatment. CONCLUSION: High energy fast neutron radiotherapy is safe and effective when adequate beam delivery systems and collimation are available, and it is significantly superior to external beam photon radiotherapy in the local-regional treatment of large prostate tumors.

Neutron vs. photon radiation therapy for inoperable regional non-small cell lung cancer: results of a multicenter randomized trial.

PURPOSE: To determine, with a prospective, multicenter randomized study, whether fast neutron radiation therapy improves the outcome for patients with non-small cell lung cancer, as compared to conventional photon radiotherapy. METHODS AND MATERIALS: From September 1986 to March 1991, a total of 200 patients with inoperable regional non-small cell lung cancer were randomized to 20.4 Gy in 12 fractions with neutrons versus 66 Gy in 33 fractions with photons. Inoperable patients with Radiation Therapy Oncology Group Stages I, II, III, or IV(M0) disease, Karnofsky Performance Score > or = 70, and who had received no previous therapy for their non-small cell lung cancer were eligible for the study. Of the 200 patients randomized, a total of 193 patients, 99 on the neutron arm and 94 on the photon arm, were eligible for analysis. The two treatment groups were balanced with regards to prognostic factors. At the time of this analysis, the median at-risk follow-up was 33 months, with a minimum follow-up of 16 months. RESULTS: No difference in overall survival was observed; however, there was a statistically significant improvement in survival for patients with squamous cell histology (p = 0.02), and a trend toward improved survival for those with favorable prognostic factors (i.e., patients who were not T4, N3, and had no pleural effusion or weight loss > 5% from baseline) (p = 0.15), favoring the neutron-treated group. With the exception of skin and subcutaneous changes, acute and late toxicity was similar in both arms. CONCLUSION: In selected patients with inoperable regional non-small cell lung cancer (e.g., squamous cell histology, favorable prognostic factors), fast neutron irradiation provides a therapeutic benefit over conventional photon radiotherapy.

Neutron versus photon irradiation for unresectable salivary gland tumors: final report of an RTOG-MRC randomized clinical trial. Radiation Therapy Oncology Group. Medical Research Council.

PURPOSE: To compare the efficacy of fast neutron radiotherapy versus conventional photon and/or electron radiotherapy for unresectable, malignant salivary gland tumors a randomized clinical trial comparing was sponsored by the Radiation Therapy Oncology Group in the United States and the Medical Research Council in Great Britain. METHODS AND MATERIALS: Eligibility criteria included either inoperable primary or recurrent major or minor salivary gland tumors. Patients were stratified by surgical status (primary vs. recurrent), tumor size (less than or greater than 5 cm), and histology (squamous or malignant mixed versus other). After a total of 32 patients were entered onto this study, it appeared that the group receiving fast neutron radiotherapy had a significantly improved local/regional control rate and also a borderline improvement in survival and the study was stopped earlier than planned for ethical reasons. Twenty-five patients were study-eligible and analyzable. RESULTS: Ten-year follow-up data for this study is presented. On an actuarial basis, there continues to be a statistically-significant p = 0.009) but there is no improvement in overall survival (15% vs. 25%, p = n.s.). Patterns of failure are analyzed and it is shown that distant metastases account for the majority of failures on the neutron arm and local/regional failures account for the majority of failures on the photon arm. Long-term, treatment-related morbidity is analyzed and while the incidence of morbidity graded "severe" was greater on the neutron arm, there was no significant difference in "life-threatening" complications. This work is placed in the context of other series of malignant salivary gland tumors treated with definitive radiotherapy. CONCLUSIONS: Fast neutron radiotherapy appears to be the treatment-of-choice for patients with inoperable primary of recurrent malignant salivary gland tumors.

Fast neutron radiotherapy for locally advanced prostate cancer. Final report of Radiation Therapy Oncology Group randomized clinical trial.

Between June 1977 and April 1983 the Radiation Therapy Oncology Group (RTOG) sponsored a Phase III randomized trial investigating the use of fast neutron radiotherapy for patients with locally advanced (Stages C and D1) adenocarcinoma of the prostate gland. Patients were randomized to receive either conventional photon radiation or fast neutron radiation used in a mixed-beam (neutron/photon) treatment schedule. A total of 91 analyzable patients were entered into the study, and the two patient groups were balanced with respect to the major prognostic variables. Actuarial curves are presented for local/regional control and "overall" survival. Ten-year results for clinically assessed local control are 70% for the mixed-beam group versus 58% for the photon group (p = 0.03) and for survival are 46% for the mixed-beam group versus 29% for the photon group (p = 0.04). This study suggests that a regional method of treatment can influence both local tumor control and survival in patients with locally advanced adenocarcinoma of the prostate gland.

Improved survival duration in patients with unresected solitary brain metastasis using accelerated hyperfractionated radiation therapy at total doses of 54.4 gray and greater. Results of Radiation Therapy Oncology Group 85-28.

BACKGROUND: Although there have been occasional reports of improved response with greater doses of irradiation for unresected brain metastases, dose escalation has not been systematically studied in a cohort of patients with solitary brain metastasis. The current study examines this group of patients to evaluate dose escalation using accelerated hyperfractionated radiation therapy (XRT) with regard to survival, patterns of failure, and toxicity. METHOD: Radiation Therapy Oncology Group (RTOG) 85-28, a Phase I/II randomized trial of accelerated hyperfractionated XRT for patients with unresected supratentorial brain metastases, enrolled 153 patients with solitary brain metastasis. Whole brain dose was 32 Gray (Gy) administered in 1.6 Gy fractions twice a day with an interfraction interval of 4-8 hours. Boost dose was escalated to total doses of 48.0, 54.4, 64.0, and 70.4 Gy. RESULTS: Acute and late toxicities were acceptable. The median survival time and 1-year survival rates were 4.9 months and 20% at 48 Gy; 5.4 months and 33% at 54.4 Gy; 7.2 months and 28% at 64 Gy; and 8.2 months and 37% at 70.4 Gy, respectively. Comparison of the upper three dose treatment arms to the 48 Gy treatment arm revealed a superior survival time with doses of 54.4 Gy and greater (P = 0.05). Improvement in neurologic function appeared to increase with dose escalation, with 25% of patients experiencing improvement at doses of 48 Gy, 38% at 54.4 Gy, 50% at 64 Gy, and 63% at 70.4 Gy (P = not significant). CONCLUSION: A radiation dose response for survival time appears to exist with the use of accelerated hyperfractionated XRT for patients with unresected solitary brain metastasis.

Logistics in designing clinical trials for etanidazole (SR 2508): an RTOG experience.

In a Phase II study of etanidazole (SR 2508), the dose of 17 x 2 g/m2 (total drug dose: 34 g/m2) was tested in 33 patients and the toxicity was deemed acceptable. A Phase III trial is now in progress comparing conventional radiotherapy with conventional radiotherapy plus etandizole (2 g/m2 i.v. 30 to 60 min before radiotherapy each Monday, Wednesday, and Friday to 34 g/m2 in 17 doses) in patients with unresectable head and neck carcinomas. A recent analysis showed only 14.7% grade 1 and 3.9% Grade 2 peripheral neuropathy. In the initial study design, 133 evaluable patients per treatment arm could achieve an 80% level of power of detecting a 15% difference in local-regional control rates between the radiotherapy arm (25% local-regional control at 2 years) and the radiotherapy plus etanidazole arm (assuming a 40% rate). Allowing for 20 ineligible cases in each arm, a total number of 306 was required. An interim analysis showed that 27% of the patients assigned to radiotherapy plus etanidazole are receiving less than 14 doses of the drug. It is assumed that less than 14 drug doses will not produce any therapeutic gain, therefore, a true 40% local-regional control rate in the radiotherapy plus etanidazole arm will be observed as a 36% rate when analyzed by assigned treatment. Using this information, the study was modified to have an 80% level of power in detecting a difference between a 25% local-regional control rate in the radiotherapy group and a 36% rate in the radiotherapy plus etanidazole group. Allowing for a 10% patient ineligibility rate, 518 patients are required. With 12 patients entered per month, it is estimated that patient accrual to this study will continue through October 1991.

The effect of local-regional control on distant metastatic dissemination in carcinoma of the head and neck: results of an analysis from the RTOG head and neck database.

A retrospective analysis of the effect of local control on the development of distant metastases was performed in 2648 patients with carcinoma of the head and neck selected from the RTOG database. The 5-year time-adjusted incidence of distant metastases was 21% for patients who were in local-regional control at 6 months after the start of treatment, compared to 38% for local-regional failure patients (p less than 0.001). The incidence of distant metastases detected between the interval of 6 months to 2.5 years after treatment was significantly increased in patients with tumors of the oral cavity, oropharynx, supraglottic larynx, and glottis who developed local-regional failure within this time period, compared to those who remained locally controlled (19% distant metastases for local-regional failure vs 7% for local-regional control (p less than 0.001)). In contrast, there as no difference in the incidence of distant metastases in patients with carcinoma of the nasopharynx or hypopharynx regardless of the local-regional disease status. A Cox proportional hazards regression analysis demonstrated that local-regional control was the most significant variable affecting the development of distant metastases, followed by tumor site, N-stage, and T-stage. For all tumor sites, except for the hypopharynx and nasopharynx, improvements in local-regional control are likely to improve survival. Tumors of the hypopharynx and nasopharynx have a higher probability of micro-metastatic dissemination at the time of initial diagnosis, and until effective methods to treat disseminated disease are developed, the effect of local control on survival will not be readily discerned.